The purpose of the proposal is to develop medical device coatings that bind and release therapeutic proteins, particularly growth factors. Specifically, we propose to systematically optimize and control growth factor binding and release using protocols that can be translated to the operating room. Bone fracture repair and reconstruction of critical-sized defects continue to present a significant challenge for orthopedists, clinicians, and maxillofacial surgeons. Specifically, craniofacial reconstruction remains difficult due to the complex geometry, the biomechanical functionality and the need to restore both aesthetics and functions. Tissue Regeneration Systems, Inc. (TRS) has developed a unique integration of designed biodegradable scaffolds with bioactive coatings capable of delivering therapeutic growth factors. These designed scaffolds offer a promising solution for difficult mandibular reconstruction challenges, as they provide the ability to fill complex geometric defects while providing biomechanical function. Bioactive coatings alone provide an osteoconductive surface for enhanced bone regeneration and can also deliver bone growth factors, including rhBMP-2. Although scaffold delivery of proteins has been a fundamental concept of regenerative medicine, the ability to achieve controlled and safe delivery from a designed 3-D scaffold remains a significant challenge. In addition, it is imperative that approaches for controlled growth factor release be easily incorporated into common surgical procedures. Perhaps the ideal growth factor delivery approach would involve a simple, intra-operative soaking process for growth factor incorporation, followed by controlled release in vivo. Toward that end, the specific goal of this phase I SBIR is to optimize the bioactive coated scaffolds for rapid, efficient intra-operative incorporation, and subsequent controlled release, of bone growth factors for maxillofacial bone regeneration. This phase I SBIR study will produce bioactive scaffolds that deliver a biologically active growth factor, which will then be used for mandibular reconstruction in an established, pre-clinical pig model in a phase II SBIR. PUBLIC HEALTH RELEVANCE: Bone healing processes are likely to benefit considerably from controlled growth factor delivery, which are not readily achievable using existing orthopedic devices. This proposal aims to establish design rules for controlled protein incorporation and release from nano-structured biomineral coatings on 3D polymeric scaffolds. The project is designed to systemically optimize rate and efficiency of protein binding and controlled release, which will allow for establishment of an 'Intra-operative'procedure for activation of 3D scaffolds that are custom- designed for maxillofacial reconstruction.